In a quadrupole mass spectrometer, a voltage (obtained by adding a direct-current voltage and a high-frequency voltage) according to a mass-to-charge ratio (m/z) of an ion to be measured is applied to a quadrupole mass filter, thereby allowing the ion to be measured to selectively pass through the quadrupole mass filter to be detected by a detector. Due to mechanical error of the quadrupole mass filter, variation in electronic circuit properties, operating environmental conditions and so on, in many cases, in a state that an ion having a target mass-to-charge ratio is controlled to selectively pass through the quadrupole mass filter, a shift occurs between the target mass-to-charge ratio and an actually detected mass-to-charge ratio of the ion.
In a mass calibration operation, as mentioned in Patent Document 1, firstly, a standard sample containing a component having a known theoretical value of mass-to-charge ratio is measured, and through a comparison between the theoretical value and a measured value of the mass-to-charge ratio at that time, a mass deviation at the mass-to-charge ratio is calculated and stored in advance in a memory as a calibration value. Then, when the target sample is measured, a control unit reads, from the memory, a calibration value that corresponds to the target mass-to-charge ratio, and uses it to correct the voltage applied to the quadrupole mass filter for the mass deviation to become zero. As a result, the ion having the target mass-to-charge ratio selectively passes through the quadrupole mass filter and reaches the detector for being detected.
By the way, in order to perform identification of a substance having a high molecular weight and structural analysis, a mass spectrometry means called MS/MS analysis is widely used. While a mass spectrometer for executing MS/MS analysis may have various constitutions, a triple quadrupole mass spectrometer is widely utilized because of its simpler structure and low lost.
As disclosed in Patent Document 2 and so on, a general triple quadrupole mass spectrometer is provided with a collision cell (collision chamber) between a quadrupole mass filter at a pre-stage (hereinafter “pre-stage quadrupole”) and a quadrupole mass filter at a post-stage (hereinafter “post-stage quadrupole”) to dissociate ions through collision induced dissociation (CID). In this collision cell, a quadrupole or multipole (more than four poles) ion guide is disposed in order to converge and transport the ions.
When various ions generated from the sample are introduced into the pre-stage quadrupole, the pre-stage quadrupole allows only ions having a specific mass-to-charge ratio to selectively pass therethrough as precursor ions. A CID gas such as argon gas is introduced into the collision cell, and the precursor ions introduced into the collision cell collide with the CID gas and dissociate, thereby generating various product ions. The precursor ions and the various product ions are converged due to an effect of a high-frequency electric field caused by the quadrupole ion guide. When the various product ions generated by CID are introduced into the post-stage quadrupole, the post-stage quadrupole allows only product ions having a specific mass-to-charge ratio to selectively pass therethrough, and the product ions capable of passing through the post-stage quadrupole reach a detector and are being detected.
With such triple quadrupole mass spectrometer, MS/MS analysis is feasible in a variety of modes such as multiple reaction monitoring (MRM) measurement, product ion scan measurement, precursor ion scan measurement, neutral loss scan measurement and so on.
In an MRM measurement, the mass-to-charge ratios of the ions capable of passing through the pre-stage quadrupole and through the post-stage quadrupole are respectively fixed, and intensity of a specific product ion with respect to a specific precursor ion is measured.
In a product ion scan measurement, while the mass-to-charge ratio of the ions passing through the pre-stage quadrupole is fixed at a certain value, the mass-to-charge ratio of the ions passing through the post-stage quadrupole is scanned in a predetermined mass-to-charge ratio range. Obtaining a mass spectrum of a product ion with respect to a specific precursor ion is thereby possible.
In a precursor ion scan measurement, in contrast to the product ion scan measurement, while the mass-to-charge ratio of the ions passing through the post-stage quadrupole is fixed at a certain value, the mass-to-charge ratio of the ions passing through the pre-stage quadrupole is scanned in a predetermined mass-to-charge ratio range. Obtaining a mass spectrum of a precursor ion that generates a specific product ion is thereby possible.
In a neutral loss scan measurement, a difference (i.e. neutral loss) between the mass-to-charge ratio of the ions passing through the pre-stage quadrupole and the mass-to-charge ratio of the ions passing through the post-stage quadrupole is maintained constant, and a mass scan is performed in the pre-stage quadrupole and the post-stage quadrupole respectively in predetermined mass-to-charge ratio ranges. Obtaining a mass spectrum of a precursor/product ion having a specific neutral loss is thereby possible.
Of course, in the triple quadrupole mass spectrometer, it is also possible to perform a normal scan measurement and a selected ion monitoring (SIM) measurement without performing CID of ions in the collision cell. In this case, neither the pre-stage quadrupole nor the post-stage quadrupole makes a selection of ions according to mass-to-charge ratio, allowing all of the ions to pass through that quadrupole.
Since the triple quadrupole mass spectrometer is provided with two quadrupole mass filters at the pre-stage and the post-stage as mentioned above, to increase selectivity of precursor ion and of product ion, it is necessary to perform mass calibrations separately and respectively at the pre-stage and at the post-stage. In a conventional triple quadrupole mass spectrometer, generally, mass calibration information for MS/MS analysis is created separately in the pre-stage quadrupole and in the post-stage quadrupole based on the measured results of MS analysis at a low scan speed using a standard sample. However, when a mass calibration is performed based on the mass calibration information obtained according to the above-mentioned method, there is a problem of an increased mass-to-charge ratio axis deviation in a mass spectrum in accordance with an increased scan speed in measuring modes such as precursor ion scan and neutral loss scan.
In addition, although an adjustment to mass resolution is performed similarly to mass calibration by utilizing measured results of MS analysis at a low scan speed using a standard sample, there are problems of reduced mass resolution in accordance with the increased scan speed in the measuring modes such as precursor ion scan and neutral loss scan (increased peak width of a peak profile with respect to one component), or of considerably reduced sensitivity for a decreased amount of ions even in the event that mass resolution is reduced.